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Publication number
JP2014500722A5
JP2014500722A5 JP2013538823A JP2013538823A JP2014500722A5 JP 2014500722 A5 JP2014500722 A5 JP 2014500722A5 JP 2013538823 A JP2013538823 A JP 2013538823A JP 2013538823 A JP2013538823 A JP 2013538823A JP 2014500722 A5 JP2014500722 A5 JP 2014500722A5
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JP
Japan
Prior art keywords
glucocerebrosidase
mutant recombinant
glucocerebrosidase protein
recombinant
protein according
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JP2013538823A
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Japanese (ja)
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JP2014500722A (en
JP6073796B2 (en
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Priority claimed from PCT/US2011/059731 external-priority patent/WO2012064709A2/en
Publication of JP2014500722A publication Critical patent/JP2014500722A/en
Publication of JP2014500722A5 publication Critical patent/JP2014500722A5/ja
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Claims (13)

次の位置:316、317、321および145の一つ以上にアミノ酸変異を含む、変異型組換えβ−グルコセレブロシダーゼタンパク質。   A mutant recombinant β-glucocerebrosidase protein comprising an amino acid mutation at one or more of the following positions: 316, 317, 321 and 145. アミノ酸変異F316AおよびL317Fを更に含む、請求項に記載の変異型組換えβ−グルコセレブロシダーゼタンパク質。 Further comprising an amino acid mutations F316A and L317F, mutant recombinant β- glucocerebrosidase protein of claim 1. 野生型組換えβ−グルコセレブロシダーゼに相対して増加した安定性を有することを特徴とする、請求項に記載の変異型組換えβ−グルコセレブロシダーゼタンパク質。 The mutant recombinant β-glucocerebrosidase protein according to claim 2 , characterized by having increased stability relative to wild-type recombinant β-glucocerebrosidase. 増加した安定性が、生理的条件におけるものである、請求項に記載の変異型組換えβ−グルコセレブロシダーゼタンパク質。 4. A mutant recombinant β-glucocerebrosidase protein according to claim 3 , wherein the increased stability is at physiological conditions. 増加した安定性が、ほぼ中性pHおよび約37℃の条件におけるものである、請求項に記載の変異型組換えβ−グルコセレブロシダーゼタンパク質。 4. The mutant recombinant β-glucocerebrosidase protein of claim 3 , wherein the increased stability is at about neutral pH and conditions of about 37 ° C. 野生型組換えβ−グルコセレブロシダーゼより少なくとも約2倍長い延長した見掛け半減期を有することを特徴とする、請求項に記載の変異型組換えβ−グルコセレブロシダーゼタンパク質。 The mutant recombinant β-glucocerebrosidase protein according to claim 2 , characterized in that it has an extended apparent half-life that is at least about two times longer than wild-type recombinant β-glucocerebrosidase. 延長した見掛け半減期が、ほぼ中性pHおよび約37℃の条件での約3時間にわたるインキュベーション後に測定される、請求項に記載の変異型組換えβ−グルコセレブロシダーゼタンパク質。 7. The mutant recombinant β-glucocerebrosidase protein of claim 6 , wherein the extended apparent half-life is measured after incubation for about 3 hours at about neutral pH and about 37 ° C. 野生型組換えβ−グルコセレブロシダーゼに相対して増加した触媒活性を保持することを特徴とする、請求項に記載の変異型組換えβ−グルコセレブロシダーゼタンパク質。 The mutant recombinant β-glucocerebrosidase protein according to claim 2 , characterized in that it retains an increased catalytic activity relative to wild-type recombinant β-glucocerebrosidase. 増加した触媒活性が、ほぼ中性pHおよび約37℃の条件での約3時間にわたるインキュベーション後に測定される、請求項に記載の変異型組換えβ−グルコセレブロシダーゼタンパク質。 9. The mutant recombinant β-glucocerebrosidase protein of claim 8 , wherein the increased catalytic activity is measured after incubation for about 3 hours at about neutral pH and about 37 ° C. 増加した触媒活性が、生理的条件で保持される、請求項に記載の変異型組換えβ−グルコセレブロシダーゼタンパク質。 The mutant recombinant β-glucocerebrosidase protein of claim 8 , wherein the increased catalytic activity is retained at physiological conditions. 請求項1〜10のいずれか1項に記載の変異型組換えβ−グルコセレブロシダーゼタンパク質および薬学的に許容しうる担体を含む組成物。A composition comprising the mutant recombinant β-glucocerebrosidase protein according to any one of claims 1 to 10 and a pharmaceutically acceptable carrier. 請求項1〜10のいずれか1項に記載の変異型組換えβ−グルコセレブロシダーゼタンパク質および薬学的に許容しうる緩衝剤を含む組成物。A composition comprising the mutant recombinant β-glucocerebrosidase protein according to any one of claims 1 to 10 and a pharmaceutically acceptable buffer. 請求項1〜10のいずれか1項に記載の変異型組換えβ−グルコセレブロシダーゼタンパク質を含む、リソソーム蓄積症を処置するための組成物。A composition for treating a lysosomal storage disease, comprising the mutant recombinant β-glucocerebrosidase protein according to any one of claims 1 to 10.
JP2013538823A 2010-11-08 2011-11-08 Mutant recombinant β-glucocerebrosidase protein with increased stability and increased retention catalytic activity Active JP6073796B2 (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US41133110P 2010-11-08 2010-11-08
US61/411,331 2010-11-08
US41218010P 2010-11-10 2010-11-10
US61/412,180 2010-11-10
PCT/US2011/059731 WO2012064709A2 (en) 2010-11-08 2011-11-08 Variant, recombinant beta-glucocerebrosidase proteins with increased stability and increased retained catalytic activity

Related Child Applications (1)

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JP2017000301A Division JP6457559B2 (en) 2010-11-08 2017-01-05 Mutant recombinant β-glucocerebrosidase protein with increased stability and increased retention catalytic activity

Publications (3)

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JP2014500722A JP2014500722A (en) 2014-01-16
JP2014500722A5 true JP2014500722A5 (en) 2014-12-25
JP6073796B2 JP6073796B2 (en) 2017-02-01

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JP2017000301A Active JP6457559B2 (en) 2010-11-08 2017-01-05 Mutant recombinant β-glucocerebrosidase protein with increased stability and increased retention catalytic activity

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US (4) US8962564B2 (en)
EP (2) EP2638152B1 (en)
JP (2) JP6073796B2 (en)
KR (1) KR101901467B1 (en)
CN (2) CN103314105B (en)
BR (1) BR112013011152A2 (en)
CA (1) CA2817011C (en)
CY (1) CY1118843T1 (en)
DK (1) DK2638152T3 (en)
ES (2) ES2604490T3 (en)
HR (1) HRP20161560T1 (en)
HU (1) HUE030932T2 (en)
LT (1) LT2638152T (en)
PL (1) PL2638152T3 (en)
PT (1) PT2638152T (en)
RS (1) RS55405B1 (en)
SI (1) SI2638152T1 (en)
SM (1) SMT201600431B (en)
WO (1) WO2012064709A2 (en)

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CA3127162A1 (en) * 2019-02-01 2020-08-06 Oxyrane Uk Ltd Glucocerebrosidase polypeptides
WO2021048034A1 (en) 2019-09-09 2021-03-18 F. Hoffmann-La Roche Ag Glucocerebrosidase mutants
JP2023535808A (en) * 2020-07-29 2023-08-21 フリーライン セラピューティクス リミテッド Mutant beta-glucocerebrosidase with improved stability
WO2023145813A1 (en) * 2022-01-31 2023-08-03 株式会社日本触媒 Protein with glucocerebrosidase activity and production method therefor
JPWO2023145814A1 (en) * 2022-01-31 2023-08-03
WO2023145812A1 (en) * 2022-01-31 2023-08-03 株式会社日本触媒 Glycosylated protein having glucocerebrosidase activity
WO2023198661A1 (en) 2022-04-12 2023-10-19 F. Hoffmann-La Roche Ag Fusion proteins targeted to the central nervous system
CN118715316A (en) * 2022-10-08 2024-09-27 凌意(杭州)生物科技有限公司 Polynucleotides for treating diseases associated with GCase deficiency

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JP2002511851A (en) 1997-04-30 2002-04-16 リージェンツ オブ ジ ユニバーシティー オブ ミネソタ Use of recombinant oligonucleobases in vivo to correct hepatocyte genetic lesions in vivo
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